Myelin (which comprises over 25% of the dry weight of brain in higher mammals) was long viewed as a metabolically inert electrical insulator serving only a passive function - to facilitate saltatory conduction. We suggest that, in contrast to this view, some components of the myelin sheath turn over rapidly and that this turnover marks some physiologically significant function(s) of myelin which is (are) partly under neuronal control. Specifically, we will test the hypotheses that the turnover of the phosphatidylinositides of myelin is a very rapid process, and that this metabolism is under neurotransmitter control. These experiments will involve incubation of brain slices with various combinations of isotopes (e.g. 32P-phosphate with either (3H)glycerol, (3H)inositol, or (3H)arachidonate) in conjunction with subcellular fractionation to identify which myelin components have been labeled. The role of putative neurotransmitters (acetylcholine, norepinephrine, etc.) in control of this turnover will be established. A correlation, or lack thereof, will be established between turnover of the phosphate group of myelin basic protein and that of the phosphate groups of polyphosphoinositides. The relationship of this turnover of phosphate groups to possible ion flux through the myelin membrane will be studied. This will involve preparation of unilamellar myelin vesicles, fusing them with planar lipid bilayers, and testing for the presence of sodium and potassium channels by measuring conductivity in the presence of such ions. The effect of phosphorylation state of phosphatidylinositides and of myelin basic protein will be correlated with this channel activity. Elucidation of a possibly active role of myelin metabolism with respect to facilitation of conduction along neuronal axons would add considerably to our knowledge of the pathophysiology of the large class of neurological disorders involving the myelin sheath.